A method developed in our laboratory for the maintenance of rodent (hamster and rat) colon in organ culture will be used in conjunction with in vivo and in vivo/in vitro systems to study the effect of sex steroids on colon carcinogenesis. Using in vivo techniques, we proposed to determine the incidence of 1,2-dimethylhydrizine (DMH)-induced colon cancer in BD-IX rats of different ages and also to measure early changes in the proliferation of colonic cells after the administration of DMH. In addition, the effect of gonadectomy on DMH-induced colon cancer in young and old rats will be determined. We will then attempt to determine the effects of gonadal hormone treatment prior to and during DMH administration on the initiation and/or growth of colon cancer in gonadectomized rats. Investigations will be made to determine the effect of DMH on the incidence of colon tumor induced transplacentally and whether gonadal hormones influence the induction in gonadectomized rats. Studies will be initiated to determine if neoplastic changes can be obtained in colon epithelium previously exposed to DMH by transplacental administration or direct in vitro application and maintained in organ culture. Furthermore, the influence of sex hormones on neoplastic changes of colon explants subjected to DMH by either transplacental administration or direct in vitro application of the carcinogen will be made. Moreover, studies to determine the influence of sex hormones upon colonic epithelial cell-DMH binding are also proposed.